3.BETA.-Hydroxysialic Acid Glycosides. I. Calcium-Binding Ability and Chemical and Enzymatic Stabilities.

Okamoto, Kaoru; Hasegawa, Taisuke; Toyomaki, Yoshio; Yamakawa, Masanori; Okukado, Nobuhisa

doi:10.1248/cpb.40.2728

Cited by 9 publications

(9 citation statements)

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“…However, participation of the deoxy (C-3) position has not been investigated in any study. In addition, it is known that the O-glycosidic linkage is stabilized dramatically by introducing an electron withdrawing substituent to the position next to the anomeric center, C-3 in sialic acid (BeMiller, 1967;Varghese et al, 1992;Okamoto et al, 1992). The acid and enzyme labile glycosidic bond of sialic acid may become resistant against these conditions, and this may lead to longer availability of drugs.…”

Section: Discussionmentioning

confidence: 99%

An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses

Guo

Sun²,

Kanie³

et al. 2002

Glycobiology

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The compound Neu5Ac3alphaF-DSPE (4), in which the C-3 position was modified with an axial fluorine atom, inhibited the catalytic hydrolysis of influenza virus sialidase and the binding activity of hemagglutinin. The inhibitory activities to sialidases were independent of virus isolates examined. With the positive results obtained for inhibition of hemagglutination and hemolysis induced by A/Aichi/2/68 virus, the inhibitory effect of Neu5Ac3alphaF-DSPE (4) against MDCK cells was examined, and it was found that 4 inhibits the viral infection with IC50 value of 5.6 microM based on the cytopathic effects. The experimental results indicate that compound 4 not only inhibits the attachment of virus to the cell surface receptor but also disturbs the release of the progeny viruses from infected cells by inhibiting both hemagglutinin and sialidase of the influenza viruses. The study suggested that the compound is a new class of bifunctional drug candidates for the future chemotherapy of influenza.

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Section: Discussionmentioning

confidence: 99%

An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses

Guo

Sun²,

Kanie³

et al. 2002

Glycobiology

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“…A.1, 2). Other applications of the 2-bromo derivatives include the synthesis of Oaryl- 285 and C-glycosides. 64 As evident from the examples discussed above, a C-3 hydroxy auxiliary does not provide efficient neighboring group participation, especially when applied to the glycosylation of secondary hydroxyls.…”

Section: -O-auxiliariesmentioning

confidence: 99%

Recent Advances in O-Sialylation

2000

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“…The presence of a C-3-hydroxyl group in N -acetylneuraminic acid derivatives has been shown to increase resistance to enzymatic hydrolysis by sialidases33 and, in some cases, may yield slight improvements in binding affinity compared to the unsubstituted parent compound9. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Structural characterisation of high affinity Siglec-2 (CD22) ligands in complex with whole Burkitt’s lymphoma (BL) Daudi cells by NMR spectroscopy

Madge

Maggioni

Pascolutti

et al. 2016

Sci Rep

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Siglec-2 undergoes constitutive endocytosis and is a drug target for autoimmune diseases and B cell-derived malignancies, including hairy cell leukaemia, marginal zone lymphoma, chronic lymphocytic leukaemia and non-Hodgkin’s lymphoma (NHL). An alternative to current antibody-based therapies is the use of liposomal nanoparticles loaded with cytotoxic drugs and decorated with Siglec-2 ligands. We have recently designed the first Siglec-2 ligands (9-biphenylcarboxamido-4-meta-nitrophenyl-carboxamido-Neu5Acα2Me, 9-BPC-4-mNPC-Neu5Acα2Me) with simultaneous modifications at C-4 and C-9 position. In the current study we have used Saturation Transfer Difference (STD) NMR spectroscopy to monitor the binding of 9-BPC-4-mNPC-Neu5Acα2Me to Siglec-2 present on intact Burkitt’s lymphoma Daudi cells. Pre-treatment of cells with periodate resulted in significantly higher STD NMR signal intensities for 9-BPC-4-mNPC-Neu5Acα2Me as the cells were more susceptible to ligand binding because cis-binding on the cell surface was removed. Quantification of STD NMR effects led to a cell-derived binding epitope of 9-BPC-4-mNPC-Neu5Acα2Me that facilitated the design and synthesis of C-2, C-3, C-4 and C-9 tetra-substituted Siglec-2 ligands showing an 88-fold higher affinity compared to 9-BPC-Neu5Acα2Me. This is the first time a NMR-based binding study of high affinity Siglec-2 (CD22) ligands in complex with whole Burkitt’s lymphoma Daudi cells has been described that might open new avenues in developing tailored therapeutics and personalised medicine.

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3.BETA.-Hydroxysialic Acid Glycosides. I. Calcium-Binding Ability and Chemical and Enzymatic Stabilities.

Cited by 9 publications

References 0 publications

An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses

An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses

Recent Advances in O-Sialylation

Structural characterisation of high affinity Siglec-2 (CD22) ligands in complex with whole Burkitt’s lymphoma (BL) Daudi cells by NMR spectroscopy

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